DOVE: Dose-Finding Study of Oral Ibrexafungep (SCY-078) vs. Oral Fluconazole in Subjects With Acute Vulvovaginal Candidiasis

• Sponsor: Scynexis, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03253094
• Collaborator: (none)
• Enrollment: 186
• Locations: 25
• Arms: 6
• Actual Duration (Months): 9.1
• Patients Per Site: 7.4
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

This is a multicenter, randomized, double-blind, double-dummy, active-controlled, dose-finding study to compare the efficacy, safety and tolerability of oral SCY-078 versus oral fluconazole in adult female subjects 18 years and older with moderate to severe Acute Vulvovaginal Candidiasis (AVVC). Approximately 180 eligible subjects (30 subjects per treatment group) will be enrolled and randomized into the study.

Condition or Disease	Intervention/Treatment	Phase
Candida Vulvovaginitis	Drug: Fluconazole; Drug: SCY-078	Phase 2

Detailed Description

This is a Phase 2, multicenter, randomized, double-blind, double-dummy, active-controlled, dose-ranging study of female subjects with moderate to severe Acute Vulvovaginal Candidiasis. Subjects will be randomized to either the investigational arm (SCY-078) with 5 different dose regiments ranging from 1 to 3 days of treatment or to the active-control arm (fluconazole) for 1 day of treatment. After randomization subjects may be seen on study Day 3 (on site visit for PK subjects) , Day 10 (±2,) and Day 25 (+4).

Study Design

• Study Type: Interventional
• Actual Enrollment: 186 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: randomized, double-blind, double-dummy, active-controlled, dose-findingrandomized, double-blind, double-dummy, active-controlled, dose-finding
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Multicenter, Randomized, Double-Blind, Double-Dummy, Active-Controlled, Dose-Finding Study to Compare the Safety and Efficacy of Oral Ibrexafungerp (SCY-078) vs. Oral Fluconazole in Subjects With Acute Vulvovaginal Candidiasis
• Actual Study Start Date: Aug 1, 2017
• Actual Primary Completion Date: May 4, 2018
• Actual Study Completion Date: May 4, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Fluconazole 150 mg/day for 1 day	Drug: Fluconazole; Oral Antifungal comparator; Other Names: Diflucan, Azole antifungal
Experimental: Ibrexafungerp 750mg 750mg QD for 1 day only	Drug: SCY-078; Investigational Antifungal; Other Names: Ibrexafungerp
Experimental: Ibrexafungerp 300mg 300mg BID for 1 day only	Drug: SCY-078; Investigational Antifungal; Other Names: Ibrexafungerp
Experimental: Ibrexafungerp 450mg 450mg BID for 1 day only	Drug: SCY-078; Investigational Antifungal; Other Names: Ibrexafungerp
Experimental: Ibrexafungerp 150mg 150mg BID for 3 days	Drug: SCY-078; Investigational Antifungal; Other Names: Ibrexafungerp
Experimental: Ibrexafungerp 300mg D1-D3 300mg BID for 3 days	Drug: SCY-078; Investigational Antifungal; Other Names: Ibrexafungerp

Outcome Measures

Primary Outcome Measures

1. Clinical Cure (Complete Resolution of Signs and Symptoms) [8-12 days]

   Measured by the percentage of subjects with clinical cure (complete resolution of signs and symptoms) at the test-of-cure (TOC) visit

Secondary Outcome Measures

1. Co-occurrence of Clinical and Mycological Cure [29 days]

   The percentage of subjects with both clinical cure and mycological eradication (negative fungal culture) the Test-of cure.

Other Outcome Measures

1. Incidence of Treatment Emergent Adverse Events [up to 29 days]

   The number of subjects with treatment related adverse events

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

1. Subject is a female of at least 18 years of age

2. Subject has a diagnosis of symptomatic AVVC at baseline including a positive microscopic examination with 10% KOH in a vaginal sample revealing yeast forms (hyphae/pseudohyphae) or budding yeasts, and vaginal pH (≤4.5)

Key Exclusion Criteria:

1. Subject has any vaginal condition other than AVVC that may interfere with the diagnosis or evaluation of response to therapy, such as suspected or confirmed concurrent causes of vulvovaginitis and/or cervicitis (mixed infection)

2. Need for systemic and/or topical (vaginal) antifungal treatment, including prescription or over-the-counter products during the study and treatment for VVC 28 days prior to randomization

3. Subject is actively menstruating at the time of the Baseline visit.

4. Subject has uncontrolled diabetes mellitus.

5. Subject has a vaginal sample with pH >4.5.

6. Subject has a history of or an active cervical/vaginal cancer.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UAB Personal Health Clinic	Birmingham	Alabama	United States	35294
2	Precision Trials AZ, LLC	Phoenix	Arizona	United States	85032
3	Women's Health Care Research Corp.	San Diego	California	United States	92111
4	Gulf Coast Research Group, LLC	Brandon	Florida	United States	33510
5	Altus Research, Inc.	Lake Worth	Florida	United States	33461
6	OB-GYN Associates of Mid-Florida P.A.	Leesburg	Florida	United States	34748
7	New Age Medical Research Corp.	Miami	Florida	United States	33186
8	Visionary Investigators Network	South Miami	Florida	United States	33160
9	Atlanta North Gynecology, P.C.	Roswell	Georgia	United States	30075
10	Cypress Medical Research Center, LLC	Wichita	Kansas	United States	67226
11	Clinical Trials Management, LLC	Covington	Louisiana	United States	70433
12	Clinical Trials Management, LLC	Metairie	Louisiana	United States	70006
13	Women Under Study, LLC	New Orleans	Louisiana	United States	70125
14	Tolan Park Medical Building	Detroit	Michigan	United States	48201
15	Consultants in Women's Healthcare, Inc.	Saint Louis	Missouri	United States	63131
16	Lawrence OB/GYN Clinical Research, LLC	Lawrenceville	New Jersey	United States	08648
17	Women's Health Research Center	Plainsboro	New Jersey	United States	08536
18	Unified Women's Clinical Research - Central Carolina	Greensboro	North Carolina	United States	27408
19	Wake Research Associates, LLC	Raleigh	North Carolina	United States	27612
20	Drexel University	Philadelphia	Pennsylvania	United States	19102
21	Medical Research South, LLC	Charleston	South Carolina	United States	29407
22	WR-Medical Research Center of Memphis, LLC	Memphis	Tennessee	United States	38120
23	Tmc Life Research, Inc.	Houston	Texas	United States	77054
24	Clinical Trials of Texas, Inc.	San Antonio	Texas	United States	78229
25	Seattle Women's Health, Research, Gynecology	Seattle	Washington	United States	98105

Sponsors and Collaborators

• Scynexis, Inc.

Investigators

• Study Director: David Angulo, MD, Scynexis, Inc.

Study Documents (Full-Text)

• Study Protocol - Jul 13, 2017
• Statistical Analysis Plan - Jun 6, 2018

More Information

Publications

None provided.

• Responsible Party: Scynexis, Inc.
• ClinicalTrials.gov Identifier: NCT03253094
• Other Study ID Numbers: SCY-078-204
• First Posted: Aug 17, 2017
• Last Update Posted: Aug 12, 2021
• Last Verified: Aug 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Candidiasis; Candidiasis, Vulvovaginal; Vulvovaginitis; Fluconazole; Ibrexafungerp

Study Results

Participant Flow

Arm/Group Title	Ibrexafungerp 750-mg	Ibrexafungerp 300-mg	Ibrexafungerp 450-mg	Ibrexafungerp 150-mg	Ibrexafungerp 300-mg (3 Days)	Fluconazole
Arm/Group Description	750 mg QD for 1 day only	300 mg BID for 1 day only	450 mg BID for 1 day only	150 mg BID for 3 days	300 mg BID for 3 days	150 mg QD for 1 day
Period Title: Overall Study
STARTED	32	30	28	32	32	32
Subjects Discontinued	4	3	6	4	5	4
COMPLETED	28	27	22	28	27	28
NOT COMPLETED	4	3	6	4	5	4

Baseline Characteristics

Arm/Group Title	Ibrexafungerp 750-mg	Ibrexafungerp 300-mg	Ibrexafungerp 450-mg	Ibrexafungerp 150-mg	Ibrexafungerp 300-mg (3 Days)	Fluconazole	Total
Arm/Group Description	750 mg QD for 1 day only	300 mg BID for 1 day only	450 mg BID for 1 day only	150 mg BID for 3 days	300 mg BID for 3 days	150 mg QD for 1 day	Total of all reporting groups
Overall Participants	32	30	28	32	32	32	186
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	34.6 (12.3)	34.4 (11.3)	34.5 (9.8)	33.3 (10.5)	32.0 (8.5)	33.8 (10.1)	33.7 (10.4)
Sex: Female, Male (Count of Participants)
Female	32 100%	30 100%	28 100%	32 100%	32 100%	32 100%	186 100%
Male	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	10 31.3%	9 30%	8 28.6%	11 34.4%	7 21.9%	11 34.4%	56 30.1%
Not Hispanic or Latino	22 68.8%	21 70%	20 71.4%	21 65.6%	25 78.1%	21 65.6%	130 69.9%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	1 3.1%	0 0%	1 3.6%	0 0%	1 3.1%	0 0%	3 1.6%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	9 28.1%	10 33.3%	12 42.9%	13 40.6%	15 46.9%	13 40.6%	72 38.7%
White	22 68.8%	20 66.7%	14 50%	18 56.3%	16 50%	19 59.4%	109 58.6%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	1 3.6%	1 3.1%	0 0%	0 0%	2 1.1%
Region of Enrollment (participants) [Number]
United States	32 100%	30 100%	28 100%	32 100%	32 100%	32 100%	186 100%

Outcome Measures

1. Primary Outcome

Title	Clinical Cure (Complete Resolution of Signs and Symptoms)
Description	Measured by the percentage of subjects with clinical cure (complete resolution of signs and symptoms) at the test-of-cure (TOC) visit
Time Frame	8-12 days

Outcome Measure Data

Analysis Population Description

mITT

Arm/Group Title	Ibrexafungerp 750-mg	Ibrexafungerp 300-mg	Ibrexafungerp 450-mg	Ibrexafungerp 150-mg	Ibrexafungerp 300-mg D1 to D3	Fluconazole
Arm/Group Description	750 mg QD D1 only	300 mg BID D1 only	450 mg BID D1 only	150 mg BID D1 to D3	300 mg BID D1 to D3	150 mg QD D1 only
Measure Participants	26	27	21	29	26	24
Clinical cure	9 28.1%	14 46.7%	13 46.4%	14 43.8%	15 46.9%	14 43.8%
Clinical failure	17 53.1%	13 43.3%	8 28.6%	15 46.9%	11 34.4%	10 31.3%

2. Secondary Outcome

Title	Co-occurrence of Clinical and Mycological Cure
Description	The percentage of subjects with both clinical cure and mycological eradication (negative fungal culture) the Test-of cure.
Time Frame	29 days

Outcome Measure Data

Analysis Population Description

mITT

Arm/Group Title	Ibrexafungerp 750-mg	Ibrexafungerp 300-mg	Ibrexafungerp 450-mg	Ibrexafungerp 150-mg	Ibrexafungerp 300-mg D1 to D3	Fluconazole
Arm/Group Description	750 mg QD D1 only	300 mg BID D1 only	450 mg BID D1 only	150 mg BID D1 to D3	300 mg BID D1 to D3	150 mg QD D1 only
Measure Participants	26	27	21	29	26	24
Clinical cure and Mycological Eradication	4 12.5%	10 33.3%	11 39.3%	8 25%	13 40.6%	10 31.3%
Clinical failure and/or mycological persistence	22 68.8%	17 56.7%	10 35.7%	21 65.6%	13 40.6%	14 43.8%

3. Other Pre-specified Outcome

Title	Incidence of Treatment Emergent Adverse Events
Description	The number of subjects with treatment related adverse events
Time Frame	up to 29 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ibrexafungerp 750-mg	Ibrexafungerp 300-mg	Ibrexafungerp 450-mg	Ibrexafungerp 150-mg	Ibrexafungerp 300-mg D1 to D3	Fluconazole
Arm/Group Description	750 mg QD D1 only	300 mg BID D1 only	450 mg BID D1 only	150 mg BID D1 to D3	300 mg BID D1 to D3	150 mg QD D1 only
Measure Participants	32	30	28	31	32	32
Treatment related Treatment-emergent adverse event	20 62.5%	14 46.7%	16 57.1%	12 37.5%	15 46.9%	8 25%
No Treatment related Treatment-emergent adverse event	12 37.5%	16 53.3%	12 42.9%	19 59.4%	17 53.1%	24 75%

Adverse Events

Time Frame	29 days
Arm/Group Title	Ibrexafungerp 750-mg		Ibrexafungerp 300-mg		Ibrexafungerp 450-mg		Ibrexafungerp 150-mg		Ibrexafungerp 300-mg D1 to D3		Fluconazole
Arm/Group Description	750 mg QD D1 only		300 mg BID D1 only		450 mg BID D1 only		150 mg BID D1 to D3		300 mg BID D1 to D3		150 mg QD D1 only
All Cause Mortality
	Ibrexafungerp 750-mg		Ibrexafungerp 300-mg		Ibrexafungerp 450-mg		Ibrexafungerp 150-mg		Ibrexafungerp 300-mg D1 to D3		Fluconazole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/32 (0%)		0/30 (0%)		0/28 (0%)		0/31 (0%)		0/32 (0%)		0/32 (0%)
Serious Adverse Events
	Ibrexafungerp 750-mg		Ibrexafungerp 300-mg		Ibrexafungerp 450-mg		Ibrexafungerp 150-mg		Ibrexafungerp 300-mg D1 to D3		Fluconazole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/32 (0%)		0/30 (0%)		0/28 (0%)		0/31 (0%)		0/32 (0%)		0/32 (0%)
Other (Not Including Serious) Adverse Events
	Ibrexafungerp 750-mg		Ibrexafungerp 300-mg		Ibrexafungerp 450-mg		Ibrexafungerp 150-mg		Ibrexafungerp 300-mg D1 to D3		Fluconazole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/32 (65.6%)		13/30 (43.3%)		15/28 (53.6%)		15/31 (48.4%)		18/32 (56.3%)		10/32 (31.3%)
Gastrointestinal disorders
Abdominal pain	5/32 (15.6%)		1/30 (3.3%)		2/28 (7.1%)		3/31 (9.7%)		0/32 (0%)		3/32 (9.4%)
Abdominal pain upper	1/32 (3.1%)		0/30 (0%)		2/28 (7.1%)		2/31 (6.5%)		3/32 (9.4%)		1/32 (3.1%)
Diarrhoea	15/32 (46.9%)		5/30 (16.7%)		6/28 (21.4%)		4/31 (12.9%)		13/32 (40.6%)		1/32 (3.1%)
Nausea	8/32 (25%)		3/30 (10%)		8/28 (28.6%)		6/31 (19.4%)		6/32 (18.8%)		2/32 (6.3%)
Vomiting	1/32 (3.1%)		0/30 (0%)		4/28 (14.3%)		0/31 (0%)		2/32 (6.3%)		0/32 (0%)
General disorders
Fatigue	0/32 (0%)		1/30 (3.3%)		0/28 (0%)		2/31 (6.5%)		2/32 (6.3%)		2/32 (6.3%)
Infections and infestations
Nasopharyngitis	0/32 (0%)		2/30 (6.7%)		0/28 (0%)		0/31 (0%)		1/32 (3.1%)		0/32 (0%)
Investigations
Blood creatine phosphokinase increased	2/32 (6.3%)		1/30 (3.3%)		0/28 (0%)		2/31 (6.5%)		0/32 (0%)		1/32 (3.1%)
Nervous system disorders
Dizziness	1/32 (3.1%)		2/30 (6.7%)		2/28 (7.1%)		3/31 (9.7%)		0/32 (0%)		0/32 (0%)
Headache	3/32 (9.4%)		3/30 (10%)		3/28 (10.7%)		9/31 (29%)		4/32 (12.5%)		2/32 (6.3%)
Somnolence	1/32 (3.1%)		0/30 (0%)		0/28 (0%)		0/31 (0%)		0/32 (0%)		2/32 (6.3%)
Skin and subcutaneous tissue disorders
Pruritus	0/32 (0%)		2/30 (6.7%)		0/28 (0%)		0/31 (0%)		0/32 (0%)		1/32 (3.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.